The present invention is directed to various methods and devices for treating skeletal and other connective tissue disorders. The methods and devices of the invention utilize isolated and culturally expanded marrow-derived mesenchymal cells which, under certain conditions, can be induced to differentiate into different types of desired connective tissue, such as into bone or cartilage forming cells.
Marrow-derived mesenchymal cells are the formative pluripotential blast cells found in the bone that are believed to be capable of differentiating into any of the specific types of connective tissues (i.e. the tissues of the body that support the specialized elements; particularly adipose, areolar, osseous, cartilaginous, elastic, and fibrous connective tissues) depending upon various environmental influences. Although these cells are normally present at very low frequencies in bone marrow, the inventors of the instant invention have discovered a process for isolating, purifying, and greatly replicating the marrow-derived mesenchymal cells in culture, i.e. in vitro. This discovery is the subject matter of a co-pending U.S. patent application.
In addition to this discovery, the inventors have also discovered that certain factors, such as mechanical, cellular, and biochemical stimuli can be utilized in order to induce differentiation of the culturally expanded marrow-derived mesenchymal cells (i.e. mesenchymal stem cells) into specific types of desired connective tissue such as bone forming cells, etc. As a result, the present invention is directed to methods of utilizing the culturally expanded marrow-derived mesenchymal cells for correcting or modifying connective tissue disorders, such as the regeneration of missing or damaged skeletal tissue, enhancing the implantation of various plastic or metal prosthetic devices through the attachment of the isolated and culturally expanded marrow-derived mesenchymal cells onto the porous surfaces of the prosthetic devices, which, upon the activation and subsequent differentiation of the marrow-derived mesenchymal cells, produce natural osseous bridges.
In addition, the present invention relates to various methods and devices for utilizing the culturally expanded marrow-derived mesenchymal cells in order to enhance hemopoietic cell production. In this regard, one embodiment of the invention is directed to methods for using composite grafts of cultured marrow-derived mesenchymal cells to augment the rate of hemopoietic cell reserve during bone marrow transplantation. An additional embodiment of the invention concerns various methods for using composite grafts of cultured marrow-derived mesenchymal cells and ceramics implanted into hosts, such as into subcutaneous sites in nude mice, as catalysts for the production of a reservoir of hemopoietic stem cells.